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Nicotine has been shown to enhance the reinforcement and reward-responsiveness of non-nicotine stimuli. To determine whether nicotine enhances the strength of conditioning to context, undergraduate participants with varying levels of nicotine dependence were recruited for a two-day study and tested on a virtual reality (VR) conditioned place preference (CPP) paradigm. On day one, participants explored two virtual rooms where they received multiple pairings of M&M rewards in one room and no rewards in the other room, followed by a free-access test session with no rewards. On day two, participants received three test sessions to assess extinction. Subsequently, participants received M&Ms. in a novel context and were then tested for reinstatement. Prior to testing on each day, subjects were administered either nicotine (4mg) or placebo lozenges, in a between-subjects, four-group, 2×2 design (nicotine or placebo on days 1 and 2). After conditioning on day one, only participants who received placebo exhibited a CPP by spending significantly more time in the room previously-paired with M&Ms. Contrary to our hypothesis, nicotine-treated participants did not display a significant CPP, and there were no significant differences between treatment groups. However, post hoc analysis indicated that in a subset of participants with greater nicotine dependence, the nicotine group displayed a CPP by rating the M&M-paired room as significantly more enjoyable than those who received placebo. Additionally, while neither treatment group showed significant place preferences during the first two extinction sessions on Day 2, individuals who received nicotine on Day 1 or placebo on Day 2 spent significantly more time in the M&M-paired room during the final extinction session. Finally, those who received nicotine on Day 2 exhibited significantly greater reinstatement compared to placebo-treated participants. These results partially support preclinical evidence that nicotine can affect learning, extinction, and reinstatement. [ABSTRACT FROM AUTHOR]

Background Cotinine is one of the major metabolites of nicotine. The aim our study was to investigate cotinine as a marker for individual risk prediction in the Ludwigshafen Risk and Cardiovascular Health study. Methods 840 samples had detectable cotinine measured using a radioimmunoassay (RIA nicotine metabolite, DPC Biermann GmbH). The distribution of risk factors across quartiles of cotinine or pack-years was analyzed by ANOVA and the association of cotinine and pack-years with mortality by Cox regression. Results Cotinine and pack-years both showed significant association with mortality in adjusted models with HRs (95% CI) of 1.30 (1.17–1.44) and 1.26 (1.13–1.42) comparing the third to the first tertile for cotinine and pack-years, respectively. Either cotinine or pack-years or self-reported smoking increased the area-under-the-curve significantly as compared to a basic model including other risk factors. Discussion Cotinine is a strong predictor of mortality in non-smokers as well as in smokers. As objectively measurable parameter cotinine would be preferable for risk prediction. [ABSTRACT FROM AUTHOR]

A reprint of the article "Nicotine and health" which was published in a 2014 issue of "Drug and Therapeutics Bulletin" is presented. It discusses the pharmacological effects of nicotine, described to be the primary addictive agent in tobacco products. Topics mentioned include nicotine and its pharmacology, the negative effects of nicotine, and harm reduction with nicotine replacement therapy (NRT). Also cited are the postulated positive effects of nicotine claimed by people who smoke.

Intermittent smokers (ITS) – who smoke less than daily – comprise an increasing proportion of adult smokers. Their smoking patterns challenge theoretical models of smoking motivation, which emphasize regular and frequent smoking to maintain nicotine levels and avoid withdrawal, but yet have gone largely unexamined. We characterized smoking patterns among 212 ITS (smoking 4–27 days per month) compared to 194 daily smokers (DS; smoking 5–30 cigarettes daily) who monitored situational antecedents of smoking using ecological momentary assessment. Subjects recorded each cigarette on an electronic diary, and situational variables were assessed in a random subset (n = 21,539 smoking episodes); parallel assessments were obtained by beeping subjects at random when they were not smoking (n = 26,930 non-smoking occasions). Compared to DS, ITS' smoking was more strongly associated with being away from home, being in a bar, drinking alcohol, socializing, being with friends and acquaintances, and when others were smoking. Mood had only modest effects in either group. DS' and ITS' smoking were substantially and equally suppressed by smoking restrictions, although ITS more often cited self-imposed restrictions. ITS' smoking was consistently more associated with environmental cues and contexts, especially those associated with positive or “indulgent” smoking situations. Stimulus control may be an important influence in maintaining smoking and making quitting difficult among ITS. [ABSTRACT FROM AUTHOR]

Classical genetic studies show the heritability of cigarette smoking is 0.4–0.6, and that multiple genes confer susceptibility and resistance to smoking. Despite recent advances in identifying genes associated with smoking behaviors, the major source of this heritability and its impact on susceptibility and resistance are largely unknown. Operant self-administration (SA) of intravenous nicotine is an established model for smoking behavior. We recently confirmed that genetic factors exert strong control over nicotine intake in isogenic rat strains. Because the processing of afferent dopaminergic signals by nucleus accumbens shell (AcbS) is critical for acquisition and maintenance of motivated behaviors reinforced by nicotine, we hypothesized that differential basal gene expression in AcbS accounts for much of the strain-to-strain variation in nicotine SA. We therefore sequenced the transcriptome of AcbS samples obtained by laser capture microdissection from 10 isogenic adolescent rat strains and compared all RNA transcript levels with behavior. Weighted gene co-expression network analysis, a systems biology method, found 12 modules (i.e., unique sets of genes that covary across all samples) that correlated (p<0.05) with amount of self-administered nicotine; 9 of 12 correlated negatively, implying a protective role. PCR confirmed selected genes from these modules. Chilibot, a literature mining tool, identified 15 genes within 1 module that were nominally associated with cigarette smoking, thereby providing strong support for the analytical approach. This is the first report demonstrating that nicotine intake by adolescent rodents is associated with the expression of specific genes in AcbS of the mesolimbic system, which controls motivated behaviors. These findings provide new insights into genetic mechanisms that predispose or protect against tobacco addiction. [ABSTRACT FROM AUTHOR]

The objectives of this study were to: (i) to develop questionnaires that can identify never-smoking children and adults experiencing increased exposure to secondhand smoke (SHS+), (ii) to determine their validity against hair nicotine, and (iii) assess their reliability. A sample of 191 children (85 males; 106 females; 7–18 years) and 95 adult (23 males; 72 females; 18–62 years) never-smokers consented to hair nicotine analysis and answered a large number of questions assessing all sources of SHS. A randomly-selected 30% answered the questions again after 20–30 days. Prevalence of SHS+ in children and adults was 0.52±0.07 and 0.67±0.10, respectively (p<0.05). The Smoke Scale for Children (SS-C) and the Smoke Scale for Adults (SS-A) were developed via factor analysis and included nine questions each. Positivity criteria for SS-C and SS-A via receiver operating characteristics curve analysis were identified at >16.5 and >16, respectively. Significant Kappa agreement (p<0.05) was confirmed when comparing the SS-C and SS-A to hair nicotine concentration. Reliability analyses demonstrated that the SS-C and SS-A scores obtained on two different days are highly correlated (p<0.001) and not significantly different (p>0.05). Area under the curve and McNemar's Chi-square showed no pair-wise differences in sensitivity and specificity at the cutoff point between the two different days for SS-C and SS-A (p>0.05). We conclude that the SS-C and the SS-A represent valid, reliable, practical, and inexpensive instruments to identify children and adult never-smokers exposed to increased SHS. Future research should aim to further increase the validity of the two questionnaires. [ABSTRACT FROM AUTHOR]

Objective: To determine if maternal use of snuff (containing high levels of nicotine, low levels of nitrosamines and no combustion products) is associated with an increased risk of oral cleft malformations in the infant and whether cessation of snuff use or smoking before the antenatal booking influences the risk. Method: A population-based cohort study was conducted on all live born infants, recorded in the Swedish Medical Birth Register from 1999 through 2009 (n = 1 086 213). Risks of oral clefts were evaluated by multivariate logistic regression analyses (using adjusted odds ratios, with 95% confidence intervals [CI]). Results: Among 975 866 infants that had information on maternal tobacco use, 1761 cases of oral clefts were diagnosed. More than 50% of the mothers who used snuff or smoked three months prior pregnancy stopped using before the antenatal booking. Almost 8% of the mothers were smoking at the antenatal booking and 1,1% of the mothers used snuff. Compared with infants of non-tobacco users, the adjusted odds ratios (95% CI) of any oral cleft for infants of mothers who continued to use snuff or to smoke were 1.48 [1.00–2.21] and 1.19 [1.01–1.41], respectively. In contrast, in infants of mothers who stopped using snuff or stopped smoking before the antenatal booking, the corresponding risks were not increased (adjusted odds ratios [95% CI] were 0.71 [0.44–1.14] and 0.88 [0.73–1.05], respectively). Conclusion: Maternal snuff use or smoking in early pregnancy is associated with an increased risk of oral clefts. Infants of mothers who stopped using snuff or stopped smoking before the antenatal booking had no increased risk of oral cleft malformations. Oral snuff or other sources of nicotine should not be recommended as an alternative for smoke-cessation during pregnancy. [ABSTRACT FROM AUTHOR]

Persons infected with HIV-1 often develop neurologic disorders despite receiving highly active anti-retroviral therapy. Although the underlying mechanism is largely undetermined, our previous RNA-seq-based study showed that the expression of many genes was altered in the central nervous system (CNS) of HIV-1 transgenic (HIV-1Tg) rats. Because nicotine, a natural agonist of nicotinic acetylcholine receptors, exhibits a neuroprotective effect, we presently tested the hypothesis that nicotine restores the expression of altered genes in the CNS of HIV-1Tg rats. Adult male HIV-1Tg and F344 control strain rats were injected with either nicotine (0.25 mg/kg) or saline subcutaneously twice a day for 17 days. Gene expression in the prefrontal cortex (PFC), dorsal hippocampus (HIP), and dorsal striatum (STR) was evaluated using the RNA deep sequencing technique. We found that about 20% of the altered genes in the HIV-1Tg rat were affected by nicotine in each brain region, with the expression of most restored. Analysis of the restored genes showed distinct pathways corrected by nicotine in different brain regions of HIV-1Tg rats. Specifically, the two most significantly restored pathways were Wnt/β-catenin signaling and ephrin B signaling in the PFC, cAMP-responsive element-binding protein (CREB) signaling and glutathione metabolism pathway in the HIP, and tricarboxylic acid (TCA) cycle and calcium signaling in the STR. Together, our findings indicate that cholinergic modulators such as nicotine have beneficial effects on HIV-1-induced neurologic deficits. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by brain accumulation of the neurotoxic amyloid-β peptide (Aβ) and by loss of cholinergic neurons and nicotinic acetylcholine receptors (nAChRs). Recent evidence indicates that memory loss and cognitive decline in AD correlate better with the amount of soluble Aβ than with the extent of amyloid plaque deposits in affected brains. Inhibition of nAChRs by soluble Aβ40 is suggested to contribute to early cholinergic dysfunction in AD. Using phage display screening, we have previously identified a heptapeptide, termed IQ, homologous to most nAChR subtypes, binding with nanomolar affinity to soluble Aβ40 and blocking Aβ-induced inhibition of carbamylcholine-induced currents in PC12 cells expressing α7 nAChRs. Using alanine scanning mutagenesis and whole-cell current recording, we have now defined the amino acids in IQ essential for reversal of Aβ40 inhibition of carbamylcholine-induced responses in PC12 cells, mediated by α7 subtypes and other endogenously expressed nAChRs. We further investigated the effects of soluble Aβ, IQ and analogues of IQ on α3β4 nAChRs recombinantly expressed in HEK293 cells. Results show that nanomolar concentrations of soluble Aβ40 potently inhibit the function of α3β4 nAChRs, and that subsequent addition of IQ or its analogues does not reverse this effect. However, co-application of IQ makes the inhibition of α3β4 nAChRs by Aβ40 reversible. These findings indicate that Aβ40 inhibits different subtypes of nAChRs by interacting with specific receptor domains homologous to the IQ peptide, suggesting that IQ may be a lead for novel drugs to block the inhibition of cholinergic function in AD. [ABSTRACT FROM AUTHOR]

Tobacco smoking is an important risk factor for the development of several cancers, osteoporosis, and inflammatory diseases such as periodontitis. Nicotine is one of the major components of tobacco. In previous study, we showed that nicotine inhibits mineralized nodule formation by osteoblasts, and the culture medium from osteoblasts containing nicotine and lipopolysaccharide increases osteoclast differentiation. However, the direct effect of nicotine on the differentiation and function of osteoclasts is poorly understood. Thus, we examined the direct effects of nicotine on the expression of nicotine receptors and bone resorption-related enzymes, mineral resorption, actin organization, and bone resorption using RAW264.7 cells and bone marrow cells as osteoclast precursors. Cells were cultured with 10−5, 10−4, or 10−3 M nicotine and/or 50 µM α-bungarotoxin (btx), an 7 nicotine receptor antagonist, in differentiation medium containing the soluble RANKL for up 7 days. 1–5, 7, 9, and 10 nicotine receptors were expressed on RAW264.7 cells. The expression of 7 nicotine receptor was increased by the addition of nicotine. Nicotine suppressed the number of tartrate-resistant acid phosphatase positive multinuclear osteoclasts with large nuclei(≥10 nuclei), and decreased the planar area of each cell. Nicotine decreased expression of cathepsin K, MMP-9, and V-ATPase d2. Btx inhibited nicotine effects. Nicotine increased CA II expression although decreased the expression of V-ATPase d2 and the distribution of F-actin. Nicotine suppressed the planar area of resorption pit by osteoclasts, but did not affect mineral resorption. These results suggest that nicotine increased the number of osteoclasts with small nuclei, but suppressed the number of osteoclasts with large nuclei. Moreover, nicotine reduced the planar area of resorption pit by suppressing the number of osteoclasts with large nuclei, V-ATPase d2, cathepsin K and MMP-9 expression and actin organization. [ABSTRACT FROM AUTHOR]

Abstract: Urinary excretion of nicotine and its five major metabolites (nicotine-N-glucuronide, cotinine, cotinine-N-glucuronide, trans-3′-hydroxycotinine, and trans-3′-hydroxycotinine-O-glucuronide), expressed as nicotine equivalents (NE), has been used as a biomarker of smoking-related nicotine exposure. In this open-label, single center study, we investigated the relationship between nicotine retention from smoking and urinary excretion of NE in adult smokers. After a 4-day washout period, 16 adult male smokers smoked 6 cigarettes per day for four consecutive days according to three predefined smoking patterns: no inhalation (Pattern A), normal inhalation (Pattern B), and deep inhalation (Pattern C). The amount of nicotine retained in the respiratory tract during smoking was estimated from the difference between the amounts of nicotine delivered and exhaled. The daily excretion of urinary NE was measured in 24h urine samples by LC–MS/MS. The mean (±S.D.) amount of nicotine retained was 0.126±0.167, 0.960±0.214, and 1.070±0.223mg/cig for Patterns A, B, and C, respectively. The mean (±S.D.) relative retention (the amount retained relative to the amount delivered) was 11.2±14.7%, 98.0±1.6%, and 99.6±0.3% for Patterns A, B, and C, respectively. On the fourth day of smoking, an average of 86±20% of the total daily amount of retained nicotine was recovered as NE in 24h urine. Nicotine equivalents was treated as a single component and the data was described by a first-order elimination pharmacokinetic model which assumed instantaneous input and distribution. Based on this model, the elimination half-life of NE was 19.4±2.6h, and the NE excretion had reached ∼96% of the steady state levels by Day 4. Our results suggest that most of the nicotine inhaled from a cigarette is retained (≥98%) in the lung, and at steady state, daily urine NE excretion reflects ∼90% of the retained nicotine dose from cigarette smoking. [Copyright &y& Elsevier]

Examines the blood nicotine and carboxyhemoglobin concentrations among smokers in Great Britain. Correlation between blood nicotine concentration and nicotine yield of cigarette; Change in the quality and carcinogenicity of tobacco tar; Amount of smoke taken in by smokers.

Focuses on medical-related issues in Great Britain. Quality of posts in clinical rheumatology; Introduction of nicotine chewing gum to the international drug market; Description of statistics methods for use in medicine.

Presents several abstracts of studies related to medicine. 'Decline in the Risk of Myocardial Infarction Among Women Who Stop Smoking,' by Lynn Rosenberg, et al; 'Nicotine and Cotinine Concentrations in the Nursing Mother and Her Infant,' by A. Dahlström, et al; 'Mechanism of Acid Reflux Associated With Cigarette Smoking,' by P.J. Kahrilas, et al.

The article describes several cases of palmoplantar pustulosis (PPP) in which dental infection is seen as a triggering factor in the induction or deterioration of the disease. It found that nicotine can affect cellular functions like induction of disturbances in polymorphic neutrophilic granulocyte chemotaxis and immunomodulation of macrophages. It cited that two cases showed extra-palmoplantar lesions which disappeared earlier than the improvement in palmoplantar lesions.

Presents news briefs related to medicine and health as of September 9, 2000. Details of a clinical trial involving melatonin as an aid to daytime sleeping; Criticism of the World Health Organization's (WHO) tobacco control record by the British American Tobacco organization; Findings of research into the molecular basis of nicotine addiction; Others.

Offers medical news updates for August 16, 2000. Study of the technique known as the 'Edmonton protocol' for transplanting insulin-producing islet cells into patients with type1 diabetes by the Immune Tolerance Network; Identification of a lung disease gene linked with primary pulmonary hypertension; Methoxsalen, which is used to treat psoriasis, as an aid to block the body's ability to metabolize nicotine; Focus of the HIV Prevention Trials Network on strategies for preventing the spread of the disease.

Presents several brief articles relating to science and medicine. Reports of at least 27 new cases of Creutzfeldt-Jakob disease in Great Britain between January and May 1998; The effects of acute nicotine withdrawl; Use of cannibis compounds for protection of neurons.

Focuses on the developments related to medicine as of September 1992. Views on the effects of cognition enhancers on the behavior of a person; Impact of nicotine on the cognition of patients with Alzheimer's disease; Opinions regarding the tutorial sessions on sports massage.